For the third time in 16 months, a Deontay Wilder opponent has tested positive for a banned substance.

The Nov. 4 heavyweight title fight between WBC titleholder Deontay Wilder and Cuban Luis Ortiz was expected to be the biggest test for the American, who has been criticized for his lack of quality opposition.

But just like Alexander Povetkin, Ortiz has likely put Wilder (38-0, 37 KO’s) in the peculiar position of trying to find a last-minute replacement.

Wilder missed out on an opportunity to fight Povetkin when the Russian tested positive for meldonium nine days before a May 2016 mandatory title defense. The fight was ultimately canceled and Wilder went on to stop Johann Duhaupas.

Then, in February, Wilder’s slated title defense against Andrzej Wawezyk was also slashed after the Pole failed a VADA test. He was replaced by Gerald Washington, who was knocked out in Round 5.

WBC President Mauricio Sulaiman revealed the news on Twitter on Thursday evening.

“@WBCBoxing has received confirmation from @Vada_Testing that Luis Ortiz has tested positive for a banned substance under [the] #CleanBoxingProgram.”

Wilder-Ortiz had the potential to be a great fight, although it would have been very difficult to surpass Anthony Joshua-Wladimir Klitschko, in April, where the unbeaten English champion got off the canvas to knock out the now-retired Wladimir Klitschko at Wembley Stadium.

Ortiz’s “A” sample tested positive for the banned diuretics chlorothiasize and hydrochlorothiazide, which can be used to mask PED use.

“I can verify the information Mauricio put out,” DiBella told ESPN. “I’m flabbergasted and particularly crestfallen for my fighter. Deontay Wilder is a great champion and a clean champion and probably has been victimized more than any other fighter in the history of the sport.”

According to an Instagram post, Ortiz and his camp picked up Losartan/HCTZ at a Walgreens pharmacy. The drug is typically prescribed to treat high blood pressure and kidney disease in patients with type 2 diabetes.